Evidence Grade C — Moderate human evidence. 14 published studies, 11 human. 9 registered clinical trials.
Medically reviewed by a licensed medical professional
Balixafortide is a synthetic peptide that blocks the CXCR4 receptor, tested as a way to sensitise breast cancer tumours to chemotherapy. A promising Phase Ib trial showed a 30% response rate, but the pivotal Phase III trial (FORTRESS) was discontinued after an interim analysis showed it was unlikely to succeed. Its clinical development for breast cancer has been abandoned.
Balixafortide is also known by these brand and alternate names:
14 published studies: 11 human, 1 animal, 0 in-vitro, 6 reviews
Balixafortide is not approved. The Phase Ib trial (54 evaluable patients) in HER2-negative metastatic breast cancer showed a 30% objective response rate when combined with eribulin chemotherapy. However, the Phase III FORTRESS trial was discontinued after interim futility analysis showed it was unlikely to meet its primary endpoint.
Balixafortide's development trajectory illustrates the challenge of translating promising Phase Ib combination therapy results into Phase III confirmation. The compound's clinical development has been discontinued.
Balixafortide blocks the CXCR4/CXCL12 signalling axis, which cancer cells use to migrate, evade immune detection, and shelter in protective tissue niches. By disrupting this signalling, the compound is proposed to expose cancer cells to chemotherapy and immune attack. The Phase Ib results suggested this mechanism could enhance chemotherapy response rates.
Research suggests the Phase Ib trial (54 patients) in metastatic breast cancer showed a 30% objective response rate when combined with chemotherapy — an encouraging signal. However, the Phase III FORTRESS trial was stopped at interim analysis for futility, definitively ending the breast cancer programme. The disconnect between promising early-phase results and Phase III failure highlights the well-known challenge of single-arm early oncology data: small, uncontrolled studies can overestimate treatment effects. The developer is evaluating alternative indications including stem cell mobilisation and haematological cancers, but no viable clinical path has been established.
PeptideTrace tracks 9 registered clinical trials for Balixafortide sourced from ClinicalTrials.gov.
Phase I Study of Cosibelimab and Balixafortide in Metastatic Pancreatic Ductal Adenocarcinoma
Tumor-Targeted-NIR-II Fluorescent Molecular Probes for the Identification of Breast Cancer Tissue and SLN Metastatic Status
POL6326 (Balixafortide) Plus Nab-paclitaxel or Eribulin in Patients With HER2-negative Advanced Breast Cancer
Pivotal Study in HER2 Negative, Locally Recurrent or Metastatic Breast Cancer
CXCR4 Antagonism for Cell Mobilisation and Healing in Acute Myocardial Infarction (CATCH-AMI)
Balixafortide (POL6326) is a synthetic cyclic peptide CXCR4 antagonist derived from horseshoe crab polyphemusin II, containing approximately 16 amino acids including D-amino acids and diaminobutyric acid residues. Molecular weight approximately 1,864 Da. Molecular formula: C84H118N24O21S2. CAS number: 1051366-32-5. Originally developed by Polyphor AG, which merged into Spexis AG in December 2021. IC50 less than 10 nM against CXCR4 with greater than 1,000-fold selectivity over CXCR7.
Research suggests balixafortide antagonizes CXCR4, disrupting the CXCR4/SDF-1 (CXCL12) signaling axis. In the oncology context, this mechanism inhibits cancer cell migration and invasion, sensitizes tumors to cytotoxic chemotherapy by mobilizing malignant cells from protective bone marrow niches, and modulates anti-tumor immune responses. The compound also mobilizes hematopoietic stem cells, providing a potential additional application in transplant medicine.
Research suggests the Phase 1b trial (Pernas et al., Lancet Oncology 2018; N=54 evaluable) showed an objective response rate of 30%, median progression-free survival of 4.5 months, and median overall survival of 16.8 months for balixafortide plus eribulin in HER2-negative metastatic breast cancer. However, the Phase 3 FORTRESS trial (NCT03786094; N=432) failed both co-primary endpoints: objective response rate 13.0% versus 13.7% for eribulin alone (P=1.00); median PFS 3.5 versus 4.0 months (HR 1.07); interim OS 11.0 versus 11.2 months (HR 1.08). No benefit was demonstrated for the combination.
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